HOUSTON ― The University of Texas MD Anderson Cancer Center’s Research Highlights showcases the latest breakthroughs in cancer care, research and prevention. These advances are made possible through seamless collaboration between MD Anderson’s world-leading clinicians and scientists, bringing discoveries from the lab to the clinic and back.
Modified drug reverses chronic pain with reduced side effects
Oxidative stress, which can cause damage to cells, is a component of many chronic diseases. Many patients are treated with NRF2 activators, which act as antioxidants to reduce chronic pain. However, NRF2 activators also come with unwanted side effects, leading Peter Grace, Ph.D., and colleagues to create a modified version of these drugs that limits off-target effects. The modified NRF2 activator was released specifically in response to oxidative stress, providing the drug exactly when and where it was needed at sites of disease. Overall, the modified NRF2 activator reduced unwanted side effects and reversed chronic pain in lab models, highlighting its therapeutic potential to improve outcomes for patients with diseases associated with oxidative stress. Learn more in Nature Biotechnology.
Phase II trial provides insights into risk stratification for patients with MDS
Patients with myelodysplastic syndrome (MDS) – a group of conditions in which bone marrow fails to produce enough healthy blood cells – often show increased activity in the IL-1β pathway, contributing to inflammation and ineffective blood cell production. In a Phase II trial, Juan Jose Rodriguez-Sevilla, M.D., Guillermo Garcia-Manero, M.D., Simona Colla, Ph.D., and colleagues evaluated the efficacy and safety of the IL-1β inhibitor canakinumab in 25 patients with lower-risk MDS who had previously received treatment. This was the first trial in which patients were followed longitudinally with single-cell analysis. The drug was safe and achieved a modest overall response rate of 17.4%, but its benefits were most evident in patients with lower genetic complexity, or fewer genetic mutations. Advanced analyses revealed that canakinumab effectively reduced inflammation and improved blood cell production in these patients, underscoring the need for personalized approaches based on genetic and molecular profiles. This study highlights the potential of targeted therapies, like canakinumab, and the importance of patient stratification for better outcomes. Learn more in Nature Communications.
Specific microRNAs shape the tumor immune microenvironment in CLL
Chronic lymphocytic leukemia (CLL) is a type of B cell blood cancer associated with certain genetic abnormalities. CLL is also known to have an immunosuppressive tumor microenvironment that promotes leukemia progression, leading Maria Teresa Bertilaccio, Ph.D., and colleagues to investigate whether there are specific genetic drivers responsible for creating this pro-tumor environment. They analyzed coding and non-coding RNA to identify microRNA changes in immune cells during CLL progression. Using lab models of CLL, they investigated what happens when those specific microRNAs are modulated and validated their findings in patient samples. Their work confirmed that a specific set of microRNAs affect how immune cells behave around cancer cells, promoting CLL progression and survival. The study highlights the role of microRNAs in shaping the immune microenvironment, emphasizing their potential as targets for personalized treatment strategies. Learn more in Blood Cancer Journal.
Chemotherapy before surgery improves outcomes for rare head and neck cancer
Patients with advanced sinonasal squamous cell carcinoma (SCC) – a rare head and neck cancer – typically are treated with surgery, but the disease is associated with poor outcomes. Thus, there is an unmet need for more effective strategies to improve disease control and organ preservation. In a Phase II trial, researchers led by Ehab Hanna, M.D., evaluated the safety and efficacy of induction chemotherapy, given before surgery, in 31 patients with stage II-IV sinonasal SCC. Patients received a combination of docetaxel, cisplatin and fluorouracil and, based on their responses, either additional chemoradiotherapy or surgery followed by radiotherapy. The overall response rate (ORR) was 82.1%, with 17.9% of patients having stable disease and none having disease progression. Grade 3 and 4 adverse events occurred in 54% and 18% of patients, respectively. The median progression-free survival was 25.8 months. Of patients alive at two years, 63% achieved organ preservation and avoided further surgeries. These results highlight pre-surgical induction chemotherapy as a promising response-directed treatment for this patient population. Learn more in Clinical Cancer Research.
PDX models accurately reflect biliary tract cancers, improving precision oncology
Biliary tract cancers (BTCs) are rare, aggressive cancers that occur when malignant cells form in the bile ducts or gallbladder, but they are understudied because of their relative scarcity. Recent studies have suggested that targeting key actionable genes with personalized treatments may improve outcomes for certain patients. Therefore, Funda Meric-Bernstam, M.D., and colleagues generated 31 novel patient-derived xenograft (PDX) models that accurately reflect the genomic profiles of BTCs. Sequencing analysis characterized each model and highlighted several actionable gene targets, including some that may be targeted with antibody-drug conjugates. Additionally, approved or investigational drugs that have previously shown clinical activity in other studies also demonstrated objective responses in these models. This is one of the largest molecularly characterized collections of BTC PDX models, and the study highlights their potential for developing personalized biomarker-selected treatment strategies to improve outcomes for patients with BTC. Learn more in Clinical Cancer Research.
In case you missed it
Read below to catch up on recent MD Anderson press releases.
- MD Anderson receives nearly $8 million in CPRIT funding for screening and early detection programs, faculty recruitment
- Healthy women have cells that resemble breast cancer, study finds
- MD Anderson Research Highlights: SITC 2024 Special Edition
- MD Anderson launches Institute for Cell Therapy Discovery & Innovation to deliver transformational new therapies
- Jennifer Bickel, M.D., named MD Anderson Vice President and Chief Wellness Officer
- Quitting smoking after cancer diagnosis improves survival across a wide variety of cancers
Read this press release in the MD Anderson Newsroom.
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